art 40 2011.propertiescalciumhydroxide
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caohTRANSCRIPT
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Review
Properties and applications of calcium hydroxide inendodontics and dental traumatology
Z. Mohammadi1 & P. M. H. Dummer21Department of Endodontics, Hamedan University of Medical Sciences, Hamedan, Iran; and 2Endodontology Research Group,School of Dentistry, Cardiff University, Cardiff, UK
Abstract
Mohammadi Z, Dummer PMH. Properties and applications
of calcium hydroxide in endodontics and dental traumatology.
International Endodontic Journal, 44, 697730, 2011.
Calcium hydroxide has been included within several
materials and antimicrobial formulations that are used
in a number of treatment modalities in endodontics.
These include, inter-appointment intracanal medica-
ments, pulp-capping agents and root canal sealers.
Calcium hydroxide formulations are also used during
treatment of root perforations, root fractures and root
resorption and have a role in dental traumatology, for
example, following tooth avulsion and luxation inju-
ries. The purpose of this paper is to review the
properties and clinical applications of calcium hydrox-
ide in endodontics and dental traumatology including
its antibacterial activity, antifungal activity, effect on
bacterial biofilms, the synergism between calcium
hydroxide and other agents, its effects on the proper-
ties of dentine, the diffusion of hydroxyl ions through
dentine and its toxicity. Pure calcium hydroxide paste
has a high pH (approximately 12.512.8) and is
classified chemically as a strong base. Its main actions
are achieved through the ionic dissociation of Ca2+
and OH) ions and their effect on vital tissues, the
induction of hard-tissue deposition and the antibacte-
rial properties. The lethal effects of calcium hydroxide
on bacterial cells are probably due to protein dena-
turation and damage to DNA and cytoplasmic mem-
branes. It has a wide range of antimicrobial activity
against common endodontic pathogens but is less
effective against Enterococcus faecalis and Candida
albicans. Calcium hydroxide is also an effective anti-
endotoxin agent. However, its effect on microbial
biofilms is controversial.
Keywords: antimicrobial, apexification, calciumhydroxide, dental traumatology, endodontics, root
resorption, vital pulp therapy.
Received 11 November 2010; accepted 29 March 2011
Introduction
Materials and therapeutic agents containing calcium
hydroxide are used extensively in a variety of treatment
modalities within endodontics and dental traumatology.
The main purpose of this article is to review the
properties and clinical applications of calcium hydrox-
ide in endodontics and dental traumatology including
its antibacterial activity, antifungal activity, effect on
bacterial biofilms, the synergism between calcium
hydroxide and other agents, its effects on the properties
of dentine, the diffusion of hydroxyl ions through
dentine, and its toxicity. The paper sets out initially to
provide the background to the main clinical applica-
tions of calcium hydroxide (Ca(OH)2) and then focuses
on its specific properties and more detailed uses.
Background
Root canal medicaments
Microorganisms are the cause of apical periodontitis
(Kakehashi et al. 1965, Moller et al. 1981, Sundqvist
Correspondence: Zahed Mohammadi, Department of Endodon-tics, Hamedan Dental School, Shahid Fahmideh Street,Hamedan, Iran (e-mail: [email protected]).
doi:10.1111/j.1365-2591.2011.01886.x
2011 International Endodontic Journal International Endodontic Journal, 44, 697730, 2011 697
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1992) and their elimination from the root canal space
during root canal treatment results in predictable
healing of apical pathosis (Bystrom & Sundqvist
1981). Indeed, many studies have demonstrated that
teeth with infected root canals at the time of canal
filling have substantially poorer outcomes than root
canals where no culturable microorganisms could be
detected (Molander et al. 2007). Unfortunately, the
complete elimination of bacteria by instrumentation
alone is unlikely to occur (Bystrom & Sundqvist
1981, Wu et al. 2006). In addition, pulp tissue
remnants may prevent microorganisms from being
entombed (Haapasalo et al. 2007) as well as have a
negative impact on the root filling in terms of its
physical properties and adaptation to the canal walls
(Wu et al. 2006). Thus, some form of irrigation and
disinfection is necessary to kill and remove microor-
ganisms, their by-products and residual tissue, as well
as remove the smear layer and other debris from the
canal system. Such chemical (therapeutic) treatments
of the root canal can be arbitrarily divided into
irrigants, canal rinses, and inter-appointment medi-
caments; calcium hydroxide is included in this latter
group.
Endodontic sealers
Sealers are responsible for the principal functions of
root fillings, which aim to prevent reinfection. That is,
sealing the root canal system by entombing remaining
bacteria and filling of irregularities in the prepared
canal system (rstavik 2005). The rationale for the
addition of calcium hydroxide to root canal sealers
eminates from observations of liners and bases con-
taining Ca(OH)2 and their antibacterial and tissue
repair abilities (rstavik 2005).
Immature teeth with open apices
The primary purpose of treating immature permanent
teeth with saveable pulps is to maintain pulp health
and allow root development to continue. Vital pulp
therapies include indirect and direct pulp-capping,
partial (superficial) pulpotomy and cervical pulpotomy.
Traditionally, mechanically exposed, but otherwise
healthy, pulps of permanent teeth have been capped
with a wound dressing containing calcium hydroxide
(Schuurs et al. 2000). In teeth with open apices and
necrotic pulps, creating a barrier across the apical
foramen is important to fill the root canal adequately.
Historically, creation of a suitable environment for the
formation of a calcified barrier involved cleaning and
shaping the canal to remove bacteria and debris
followed by placement of a calcium hydroxide paste
to fill the canal system for 624 months (Frank 1966).
Traumatology
Dental trauma involves damage to teeth and the
supporting tissues. Intracanal medicaments containing
calcium hydroxide are used to control internal resorp-
tion (Haapasalo & Endal 2006) as well as inflammatory
apical root resorption (Majorana et al. 2003). Further-
more, the International Association of Dental Trauma-
tology (2007) guidelines recommend that any tooth
with a necrotic pulp associated with a luxation injury
should be dressed with a calcium hydroxide medica-
ment until the root canal is filled. For avulsion injuries,
the use of calcium hydroxide medicament is recom-
mended for up to 1 month (Kawashima et al. 2009).
Retrieval of literature
A Medline search was performed from 1971 to the end
of 2009 and was limited to English-language papers.
The keywords searched on Medline were calcium
hydroxide AND endodontics (1943), calcium hydrox-
ide AND Enterococcus faecalis (134), calcium hydrox-
ide AND Candida albicans (51), calcium hydroxide
AND endotoxin (23), calcium hydroxide AND dentine
(986), calcium hydroxide AND biofilm (17), calcium
hydroxide AND sodium hypochlorite (174), calcium
hydroxide AND chlorhexidine (145), calcium hydr-
oxide AND vital pulp therapy (121), calcium hydrox-
ide AND apexification (138), calcium hydroxide AND
root fracture (59), calcium hydroxide AND root
resorption (203), calcium hydroxide AND perforation
(32) and calcium hydroxide AND avulsion (73).
Then, the reference section of each of those articles was
studied to find other suitable sources. The number of
retrieved papers was presented in the parentheses.
Characteristics of calcium hydroxide
Chemical composition and activity
Calcium hydroxide was introduced to endodontics as a
direct pulp-capping agent (Hermann 1920). It is a
white odourless powder with the chemical formula
Ca(OH)2 and a molecular weight of 74.08 (Farhad &
Mohammadi 2005). It has low solubility in water
(around 1.2 g L)1 at 25 !C), which decreases with arise in temperature (Siqueira & Lopes 1999). It has
been demonstrated that the dissociation coefficient of
Ca(OH)2 (0.17) controls the slow release of both
Calcium hydroxide in endodontics and dental traumatology Mohammadi & Dummer
International Endodontic Journal, 44, 697730, 2011 2011 International Endodontic Journal698
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calcium and hydroxyl ions (Rehman et al. 1996). This
low solubility is a useful clinical characteristic as an
extended period is necessary before it becomes solubi-
lized when in direct contact with fluids from vital
tissues (Spangberg & Haapasalo 2002). The pure
powder has a high pH (approximately 12.512.8)
and is insoluble in alcohol (Farhad & Mohammadi
2005). The material is chemically classified as a strong
base, its main actions come from the ionic dissociation
of Ca2+ and OH) ions and their effect on vital tissues,
generating the induction of hard-tissue deposition and
being antibacterial (Siqueira & Lopes 1999).
According to Rehman et al. (1996), Ca(OH)2 disso-
ciates into calcium and hydroxyl ions on contact with
aqueous fluids. Estrela & Pesce (1996) analysed chem-
ically the liberation of calcium and hydroxyl ions from
Ca(OH)2 pastes with vehicles of different acidbase and
hydrosolubility characteristics in the connective tissues
of dogs. Taking into account the molecular weight of
calcium hydroxide (74.08), the percentage of hydroxyl
ions is 45.89%, whilst 54.11% corresponds to the
calcium ions (Estrela & Pesce 1996). Ca(OH)2 in water
has a thixotropic behaviour and will be fluid when
agitated (Spangberg & Haapasalo 2002).
When Ca(OH)2 is exposed to carbon dioxide (CO2) or
carbonate ions (CO3)) in biological tissue, its dissoci-
ation leads to the formation of calcium carbonate
(CaCO3) and an overall consumption of Ca2+ ions.
However, it has been shown that after 30 days of
exposure to carbon dioxide, six preparations of
Ca(OH)2 maintained a purportedly bactericidal pH
within the root canal (Estrela & Pesce 1997). Estrela
& Pesce (1997) analysed chemically the formation of
calcium carbonate in the connective tissue of dogs and
showed that when saline vehicles were used with
Ca(OH)2 in a paste, the rate of formation of calcium
carbonate was practically unaltered. Estrela & Bam-
mann (1999) evaluated the presence of calcium
carbonate in samples of Ca(OH)2 stored for 2 years in
containers under varying conditions. They determined
CaCO3 by means of volumetric analysis of neutraliza-
tion, using hydrochloric acid, and visualization with
methyl orange and phenolphthalein. The level of
Ca(OH)2 converted into calcium carbonate ranged
from 5 1% to 11 1% and was not sufficient to
interfere with its properties.
In summary, calcium hydroxide is a white odourless
powder and is chemically classified as a strong base; in
contact with aqueous fluids, it dissociates into calcium
and hydroxyl ions.
Mode of action
Depending on its application, the mode of action of
Ca(OH)2 may vary.
Antimicrobial activity
The antimicrobial activity of Ca(OH)2 is related to the
release of hydroxyl ions in an aqueous environment
(Siqueira 2001). Hydroxyl ions are highly oxidant free
radicals that show extreme reactivity with several
biomolecules. This reactivity is high and indiscrimi-
nate, so this free radical rarely diffuses away from sites
of generation (Siqueira & Lopes 1999). The lethal
effects of hydroxyl ions on bacterial cells are probably
due to the following mechanisms (Siqueira & Lopes
1999):
damage to the bacterial cytoplasmic membrane; protein denaturation; and damage to the DNA.Although scientific evidence suggests that these
three mechanisms may occur, it is difficult to establish,
in a chronological sense, which is the main mechanism
involved in the death of bacterial cells after exposure to
a strong base (Siqueira & Lopes 1999). Estrela et al.
(1994) studied the biological effect of pH on the
enzymatic activity of anaerobic bacteria and concluded
that hydroxyl ions from Ca(OH)2 developed their
mechanism of action in the cytoplasmic membrane.
This membrane is responsible for essential functions
such as metabolism, cellular division and growth, and
it takes part in the final stages of cellular wall
formation, biosynthesis of lipids, transport of electrons
and oxidative phosphorylation. Extracellular enzymes
act on nutrients, carbohydrates, proteins and lipids
that, through hydrolysis, favour digestion. Intracellular
enzymes located in the cell favour respiratory activity of
the cellular wall structure. The pH gradient of the
cytoplasmic membrane is altered by the high concen-
tration of hydroxyl ions from calcium hydroxide acting
on the proteins of the membrane (protein denatur-
ation). The high pH of Ca(OH)2 alters the integrity of
the cytoplasmic membrane through chemical injury to
the organic components and transport of nutrients or
by means of the destruction of phospholipids or
unsaturated fatty acids of the cytoplasmic membrane,
observed in the peroxidation process, which is a
saponification reaction (Estrela et al. 1999).
Adjustment of intracellular pH is influenced by
several cellular processes such as the following:
cellular metabolism;
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2011 International Endodontic Journal International Endodontic Journal, 44, 697730, 2011 699
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alterations in shape, mobility, adjustment of trans-porters and polymerization of cytoskeleton compo-
nents;
activation of cellular proliferation and growth; conductivity and transport through the membrane;
and
isosmotic cellular volume.Thus, many cellular functions can be affected by pH,
including the enzymes that are essential for cellular
metabolism (Putnam 1995). Estrela et al. (1998) found
that bacterial enzymatic inactivation under extreme
conditions of pH for a long period of time was
irreversible.
In summary, the antimicrobial activity of Ca(OH)2 is
related to the release of highly reactive hydroxyl ions in
an aqueous environment, which mainly affects cyto-
plasmic membranes, proteins and DNA.
Mineralization activity
When used as a pulp-capping agent and in apexifica-
tion cases, a calcified barrier may be induced by
calcium hydroxide (Eda 1961). Because of the high pH
of pure calcium hydroxide, a superficial layer of
necrosis occurs in the pulp to a depth of up to 2 mm
(Estrela & Holland 2009). Beyond this layer, only a
mild inflammatory response is seen and, provided the
operating field is kept free from bacteria when the
material was placed, hard tissue may be formed (Estrela
et al. 1995). However, commercial products containing
Ca(OH)2 may not have such an alkaline pH.
The hydroxyl group is considered to be the most
important component of Ca(OH)2 as it provides an
alkaline environment, which encourages repair and
active calcification. The alkaline pH induced not only
neutralizes lactic acid from osteoclasts, thus preventing
dissolution of the mineral components of dentine, but
could also activate alkaline phosphatases that play an
important role in hard-tissue formation (Estrela et al.
1995). The pH necessary for the activation of this
enzyme varies from 8.6 to 10.3, according to the type
and concentration of substratum, temperature and
source of enzymes (Estrela et al. 1999). Alkaline
phosphatase is a hydrolytic enzyme that acts by means
of the liberation of inorganic phosphatase from the
esters of phosphate. It can separate phosphoric esters,
freeing phosphate ions, which then react with calcium
ions from the bloodstream to form a precipitate,
calcium phosphate, in the organic matrix. This precip-
itate is the molecular unit of hydroxyapatite (Seltzer &
Bender 1975), which is believed to be intimately
related to the process of mineralization.
Ca(OH)2 in direct contact with connective tissue
gives rise to a zone of necrosis, altering the physico-
chemical state of inter-cellular substance which,
through rupture of glycoproteins, determines protein
denaturation. The formation of mineralized tissue
following contact between Ca(OH)2 and connective
tissue has been observed from the 7th to the 10th day
following application (Holland 1971). Holland (1971)
also reported the existence of massive granulation in
the superficial granulosis zone interposed between the
zone of necrosis and the deep granulosis zone. These
structures are composed of calcium salts and calcium
protein complexes and are birefringent to polarized
light, reacting positively to chloramilic acid and to Van
Kossas method, proving that part of the calcium ions
come from the protective material. Below the deep
granulation zone is the proliferation cellular zone
and the normal pulp. Holland et al. (1999) evaluated
the reaction of rat subcutaneous connective tissue to
the implantation of dentine tubes filled with Ca(OH)2.
At the tube openings, there were Von Kossa-positive
granules that were birefringent to polarized light. Next
to these granulations, there was irregular tissue
resembling a bridge that was Von-Kossa positive in
the walls of dentinal tubules a structure highly
birefringent to polarized light appeared as a layer at
different depths.
In summary, the mineralizing action of Ca(OH)2 is
directly influenced by its high pH. The alkaline pH not
only neutralizes lactic acid from osteoclasts, but could
also activate alkaline phosphatases, which play an
important role in hard-tissue formation.
Effect of liquid vehicle
The vehicles mixed with Ca(OH)2 powder play an
important role in the overall dissociation process
because they determine the velocity of ionic dissocia-
tion causing the paste to be solubilized and resorbed at
various rates by the periapical tissues and from within
the root canal. The lower the viscosity, the higher will
be the ionic dissociation. The high molecular weight of
common vehicles minimizes the dispersion of Ca(OH)2into the tissues and maintains the paste in the desired
area for longer periods of time (Athanassiadis et al.
2007).
There are three main types of vehicles:
1. Water-soluble substances such as water, saline,
anaesthetic solutions, carboxymethylcellulose,
methylcellulose and Ringers solution.
2. Viscous vehicles such as glycerine, polyethylene-
glycol (PEG) and propylene glycol.
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International Endodontic Journal, 44, 697730, 2011 2011 International Endodontic Journal700
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3. Oil-based vehicles such as olive oil, silicone oil,
camphor (the oil of camphorated parachlorophenol),
some fatty acids (including oleic, linoleic, and isostearic
acids), eugenol and metacresylacetate (Fava & Saun-
ders 1999).
Ca(OH)2 should be combined with a liquid vehicle
because the delivery of dry Ca(OH)2 powder alone is
difficult, and fluid is required for the release of hydroxyl
ions. Sterile water or saline are the most commonly
used carriers. Aqueous solutions promote rapid ion
liberation and should be used in clinical situations.
Although dental local anaesthetic solutions have an
acidic pH (between 4 and 5), they provide an adequate
vehicle because Ca(OH)2 is a strong base, which is
affected minimally by acid (Athanassiadis et al. 2007).
The effects of glycerine and propylene glycol vehicles
on the pH of Ca(OH)2 preparations were investigated
using conductivity testing by Safavi & Nakayama
(2000). A range of 1030% for a glycerine/water
mixture and 1040% for a propylene glycol/water
mixture resulted in the greatest conductivity. They
reported that a higher concentration of these vehicles
may decrease the effectiveness of Ca(OH)2 as a root
canal medicament (Safavi & Nakayama 2000). Viscous
vehicles are also water-soluble substances that release
calcium and hydroxyl ions more slowly and for longer
periods (Gomes et al. 2002). A viscous vehicle may
remain within root canals for several months, and
hence the number of appointments required to change
the dressing will be reduced (Fava & Saunders 1999).
In addition to the type of vehicle used, the viscosity of
the paste can influence antimicrobial activity, espe-
cially for Ca(OH)2. Behnen et al. (2001) reported that
thick mixtures of Ca(OH)2 and water (1 g mL)1 H2O)
resulted in a significant reduction in antibacterial
activity against E. faecalis in dentine tubules compared
to a thin mix and the commercial product Pulpdent
paste (Pulpdent Corporation, Watertown, MA, USA).
Oily vehicles have restricted applications as they are
difficult to remove and leave a residue on the canal
walls. The difficulty of removing them from the canal
walls will affect the adherence of sealer or other
materials used to fill the canal (Fava & Saunders
1999); they are not recommended.
Polyethylene glycol (PEG) is one of the most
commonly used vehicles in root canal medicaments,
and it possesses an ideal array of properties including
low toxicity, high solubility in aqueous solutions and
low immunogenicity and antigenicity (Athanassiadis
et al. 2007). Concentrated PEG 400 solutions have
their own substantial antibacterial activity against
various pathogenic bacteria including Klebsiella pneu-
moniae, Pseudomonas aeruginosa, Eschericha coli and
Staphylococcus aureus, which is in addition to any other
substances added to the PEG base as a medicament
(Chirife et al. 1983). In a study by Camoes et al. (2003)
the pH in an aqueous medium was tested outside the
roots of human teeth when various vehicles (aqueous
or viscous) were used with Ca(OH)2. They reported that
vehicles with glycerine and PEG 400 had a tendency to
acidification during the first 8 days (pH 6.85 to 6.4
PEG 400) but then the pH returned to the levels of the
other groups after 42 days (pH 7.1 PEG 400).
In summary, the vehicle to which calcium hydroxide
is added affects the physical and chemical properties of
the compound and therefore its clinical applications.
Compared with water-soluble agents, viscous and oily
vehicles prolong the action of the calcium hydroxide
but can have associated negative side effects.
Calcium hydroxide when used inmedicaments during root canal treatment
Definition of a medicament
A medicament is an antimicrobial agent that is placed
inside the root canal between treatment appointments
in an attempt to destroy remaining microorganisms
and prevent reinfection (Weine 2004). Thus, they may
be utilized to kill bacteria, reduce inflammation (and
thereby reduce pain), help eliminate apical exudate,
control inflammatory root resorption and prevent
contamination between appointments (Farhad & Mo-
hammadi 2005). When intracanal medicaments were
not used between appointments, bacterial numbers
increased rapidly (Bystrom & Sundqvist 1981).
Anti-bacterial activity
Calcium hydroxide will exert an antibacterial effect in
the root canal system as long as a high pH is
maintained (Siqueira & Lopes 1999). In their in vivo
study, Bystrom et al. (1985) reported that root canals
treated with Ca(OH)2 had fewer bacteria than those
dressed with camphorated phenol or camphorated
monochlorophenol (CMCP). They attributed this to
the fact that Ca(OH)2 could be packed into the root
canal system allowing hydroxyl ions to be released over
time. Stevens & Grossman (1983) also reported
Ca(OH)2 to be effective in preventing the growth of
microorganisms but to a limited extent when compared
to CMCP, stressing the necessity of direct contact to
Mohammadi & Dummer Calcium hydroxide in endodontics and dental traumatology
2011 International Endodontic Journal International Endodontic Journal, 44, 697730, 2011 701
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achieve the optimum antibacterial effect. Sjogren et al.
(1991) demonstrated that a 7-day application of a
Ca(OH)2 medicament was sufficient to reduce canal
bacteria to a level that gave a negative culture. Han
et al. (2001) found that aqueous Ca(OH)2 paste and
silicone oil-based Ca(OH)2 paste were effective in the
elimination of E. faecalis in dentinal tubules. Shuping
et al. (2000) showed that placement of Ca(OH)2 for at
least 1 week rendered 92.5% of canals bacteria free.
Estrela et al. (2001) assessed two methods for deter-
mining the antimicrobial effectiveness of (i) Ca(OH)2 in
saline, (ii) Ca(OH)2 in polyethylene glycol and (iii)
Ca(OH)2 in CMCP. They concluded that both the direct
exposure test and agar diffusion test (ADT) were useful
in establishing the antimicrobial spectrum of Ca(OH)2and for developing improved infection control proto-
cols. A complete antimicrobial effect was observed after
48 h in both tests, irrespective of the Ca(OH)2 paste
vehicle. Behnen et al. (2001) demonstrated that
Ca(OH)2 decreased the numbers of E. faecalis at all
depths within dentinal tubules up to 24 h and that less
viscous preparations of Ca(OH)2 were more effective in
the elimination of E. faecalis from dentinal tubules than
viscous preparations.
In a study to evaluate the effect of electrophoretically
activated Ca(OH)2 on bacterial viability in dentinal
tubules, Lin et al. (2005) reported that treatment with
electrophoresis was significantly more effective than
pure Ca(OH)2 up to depths of 200500 lm. Specimenstreated with electrophoretically activated Ca(OH)2revealed no viable bacteria in dentinal tubules to a
depth of 500 lm from the root canal space within7 days.
Portenier et al. (2005) concluded that E. faecalis cells
in the exponential growth phase were the most
sensitive to Ca(OH)2 and were killed within 3 s to
10 min. Cells in a stationary phase were more resis-
tant, with living cells being recovered at 10 min.
However, cells in a starvation phase were the most
resistant and were not totally eliminated during the
10-min test period.
By contrast, several studies have attested to the
ineffectiveness of Ca(OH)2 in eliminating bacterial cells.
DiFiore et al. (1983) reported that Ca(OH)2 had no
antibacterial effect as a paste or as the commercial
preparation, Pulpdent, when used against S. Sanguis,
findings that were confirmed by Siqueira et al. (1998).
Haapasalo & rstavik (1987) reported that a Ca(OH)2paste (Calasept; Speiko, Darmstadt, Germany) failed to
eliminate, even superficially, E. faecalis in dentinal
tubules. Safavi et al. (1990) demonstrated that
E. faecium remained viable in dentinal tubules after
relatively extended periods of Ca(OH)2/saline mixture
treatment. rstavik & Haapasalo (1990) observed that
Ca(OH)2 could take up to 10 days to disinfect dentinal
tubules infected by facultative bacteria. Siqueira &
Uzeda (1996) demonstrated that Ca(OH)2 mixed with
saline was ineffective in eliminating E. faecalis and
E. faecium inside dentinal tubules after 1 week of
contact. Estrela et al. (1999) found that Ca(OH)2 in
infected dentinal tubules had no antimicrobial effect on
S. faecalis, S. aureus, B. subtilis, P. aeruginosa or on the
bacterial mixture used throughout the experiment.
Waltimo et al. (2005) found that a Ca(OH)2 dressing
between appointments did not have the expected effect
in terms of disinfection of the root canal system nor the
treatment outcome. Weiger et al. (2002) concluded
that the viability of E. faecalis in infected root dentine
was not affected by Ca(OH)2. In a systematic review to
assess the antibacterial efficacy of Ca(OH)2, Sathorn
et al. (2007) evaluated eight clinical trials including
257 cases. They concluded that Ca(OH)2 had limited
effectiveness in eliminating bacteria from human root
canals when assessed by culture techniques.
In a polymerase chain reaction study (PCR), the
effect of root filling with or without prior Ca(OH)2 or
2% chlorhexidine (CHX) on the persistence of bacterial
DNA in infected dentinal tubules was evaluated (Cook
et al. 2007). The report indicated that 2% CHX
treatment followed by canal filling was more effective
in removing the DNA of E. faecalis than placement of
Ca(OH)2 or immediate canal filling. Using an agar
diffusion method, Ballal et al. (2007) found that 2%
CHX gel was a more effective medicament than
Ca(OH)2 paste against E. faecalis. Krithikadatta et al.
(2007) reported that, as an intracanal medicament, 2%
CHX gel alone was more effective against E. faecalis
when compared to Ca(OH)2. Lee et al. (2008) con-
cluded that a polymeric CHX-controlled release device
(PCRD) was significantly more effective in reducing
intradentinal bacteria than Ca(OH)2.
In summary, although some clinical studies have
supported the efficacy of calcium hydroxide as an
intracanal medicament, other studies have questioned
its efficacy and indicated CHX instead of calcium
hydroxide.
Anti-endotoxin activity
Endotoxin, a part of the cell wall of all Gram-negative
bacteria, is composed of polysaccharides, lipids and
proteins and is referred to as lipopolysaccharide (LPS),
Calcium hydroxide in endodontics and dental traumatology Mohammadi & Dummer
International Endodontic Journal, 44, 697730, 2011 2011 International Endodontic Journal702
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emphasizing its chemical structure (Westphal 1975,
Rietschel & Brade 1992). Lipid A is the region of the
endotoxin molecule responsible for its toxic effects.
When free to act, endotoxins do not cause cell or tissue
pathosis directly, but they stimulate competent cells to
release chemical mediators (Leonardo et al. 2004).
Macrophages are the main target of endotoxins (Leo-
nardo et al. 2004), which, therefore, are not intrinsi-
cally toxic.
Endotoxin (LPS) is released during multiplication or
bacterial death causing a series of biological effects
(Barthel et al. 1997), which lead to an inflammatory
reaction (Rietschel & Brade 1992) and periapical bone
resorption (Stashenko 1990, Yamasaki et al. 1992).
Endotoxins from vital or nonvital, whole or fragmented
bacteria act on macrophages, neutrophils and fibro-
blasts, leading to the release of a large number of
bioactive or cytokine chemical inflammatory media-
tors, such as tumour necrosis factor (TNF), interleukin-
1 (IL-1), IL-5, IL-8, alpha-interferon and prostaglandins
(Leonardo et al. 2004).
Currently, one of the concerns in endodontics is the
treatment of teeth with necrotic pulps and periapical
pathosis because post-treatment disease persists more
often than in cases without periapical disease (Leo-
nardo et al. 1993, Katebzadeh et al. 1999). In teeth
with chronic periapical lesions, there is a greater
prevalence of Gram-negative anaerobic bacteria dis-
seminated throughout the root canal system (dentinal
tubules, apical resorptive defects and cementum lacu-
nae), including apical bacterial biofilm (Leonardo et al.
1993, Katebzadeh et al. 1999, Nelson-Filho et al.
2002, Trope et al. 1999). Because these areas are
not reached by instrumentation, the use of a root canal
medicament is recommended to aid in the elimination
of these bacteria and thus increase the potential for
clinical success (Leonardo et al. 1993, Katebzadeh
et al. 1999, Nelson-Filho et al. 2002). Teeth with and
without radiographic evidence of periapical disease
could be considered as different pathological entities
requiring different treatment regimens. Where bone
loss has occurred, the use of a root canal medicament
between treatment sessions is recommended by some
(Leonardo et al. 2000a), because the success of treat-
ment in cases with periapical pathosis is directly
related to the elimination of bacteria, products and
subproducts from the root canal system. The proce-
dures and medicaments used in root canal treatment
should not only lead to bacterial death, but also to the
inactivation of bacterial endotoxin (Leonardo et al.
2004).
In a laboratory study, Safavi & Nichols (1993)
evaluated the effect of Ca(OH)2 on bacterial LPS and
concluded that it hydrolysed the highly toxic lipid A
molecule that is responsible for the damaging effects of
endotoxin. In another study, they found that Ca(OH)2transformed lipid A into fatty acids and amino sugars,
which are atoxic components (Safavi & Nichols 1994).
These results were confirmed in studies by Barthel et al.
(1997) and Olsen et al. (1999) who reported that
Ca(OH)2 detoxifies bacterial LPS in vitro.
Nelson-Filho et al. (2002) carried out an in vivo study
to evaluate radiographically the effect of endotoxin plus
Ca(OH)2 on the periapical tissues of dogs teeth. They
observed that endotoxin caused the formation of
periapical lesions after 30 days and that Ca(OH)2inactivated bacterial LPS. Silva et al. (2002) analysed
histopathologically periapical tissues of teeth in dogs in
which the root canals were filled with bacterial LPS and
Ca(OH)2. They reported that LPS caused the formation
of periapical lesions and that Ca(OH)2 detoxified this
endotoxin in vivo. Tanomaru et al. (2003) evaluated
the effect of biomechanical preparation using different
irrigating solutions and a Ca(OH)2-based root canal
dressing in a dog experimental tooth model containing
endotoxin. Biomechanical preparation with only irri-
gating solutions did not inactivate the endotoxin;
however, the same treatment associated with the use
of the Ca(OH)2 dressing was effective in the inactivation
of the toxic effects of this endotoxin. Jiang et al. (2003)
also evaluated the direct effects of LPS on osteoclasto-
genesis and the capacity of Ca(OH)2 to inhibit the
formation of osteoclasts stimulated by endotoxin. They
reported that Ca(OH)2 significantly reduced osteoclast
differentiation. Buck et al. (2001) found that long-term
Ca(OH)2 as well as 30-min exposure to an alkaline
mixture of CHX, ethanol and sodium hypochlorite did
detoxify LPS molecules by hydrolysis of ester bonds in
the fatty acid chains of the lipid A moiety.
In summary, endotoxin, a component of the cell wall
of Gram-negative bacteria, plays a fundamental role in
the genesis and maintenance of periapical lesions
because of the induction of inflammation and bone
resorption. Ca(OH)2 inactivates endotoxin, in vitro and
in vivo, and appears currently the only clinically
effective medicament for inactivation of endotoxin.
A recent concern indirectly related to the use of
Ca(OH)2 as a medicament and the outcome of treatment
has focused on the limitations of conventional radio-
graphic techniques. Post-treatment apical periodontitis
with bone loss may not result in a visible apical
radiolucency on a conventional or digital film,
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depending on the density and thickness of the overlying
cortical bone, and the distance between the lesion and
the cortical bone. When a bone lesion is within the
cancellous bone and the overlying cortical bone is
substantial, the bone lesion may not be visible radio-
graphically (Stabholz et al. 1994, Ricucci & Bergenholtz
2003). Therefore, post-treatment apical periodontitis
can be radiographically visible or invisible. Clinically, it
has been reported that a large lesion of up to 8 mm in
diameter can be present without radiolucency (Wu et al.
2006). Thus, it now appears that conventional radio-
graphic techniques lack sufficient sensitivity to serve as
a reliable means for diagnosing post-treatment health.
Therefore, the absence of radiolucency does not prove
that residual bacteria have been entombed in the canal
system by the placement of a root filling and thus
rendered harmless. It should be noted that cone-beam
computed tomography (CBCT) provides higher detec-
tion rates than conventional and digital radiographs for
visualization of periapical lesions (Scarfe et al. 2009).
Anti-fungal activity
Fungi constitute a small proportion of the oral micro-
biota and are largely restricted to Candida albicans
(Siqueira & Sen 2004). C. albicans is the fungal species
most commonly detected in the oral cavity of both
healthy (Arendorf & Walker 1980, Lucas 1993) and
medically compromised individuals (Dupont et al.
1992). The incidence of C. albicans in the oral cavity
has been reported to be 3045% in healthy adults
(Arendorf & Walker 1980, Lucas 1993) and 95% in
patients infected with human immunodeficiency virus
(Dupont et al. 1992). Fungi have occasionally been
found in primary root canal infections (Baumgartner
et al. 2000, Lana et al. 2001), but they are more
common in filled root canals in teeth that have become
infected some time after treatment or in those that have
not responded to treatment (Siqueira & Sen 2004).
Overall, the occurrence of fungi reported in infected
root canals varies between 1% and 17% (Waltimo et al.
2004). A large number of other yeasts have also been
isolated from the oral cavity, including C. glabrata,
C. guilliermondii, C. parapsilosis, C. krusei, C. inconspicua,
C. dubliniensis, C. tropicalis and Saccharomyces species
(Siqueira & Sen 2004).
Waltimo et al. (1999a) reported that C. albicans cells
were highly resistant to Ca(OH)2 and that all Candida
species (C. albicans, C. glabrata, C. guilliermondii, C. krusei
and C. tropicalis) were either equally high or had higher
resistance to aqueous calcium hydroxide than did
E. faecalis (Waltimo et al. 1999b). Because C. albicans
survives in a wide range of pH values, the alkalinity of
saturated Ca(OH)2 solution may not have any effect on
C. albicans. In addition, Ca(OH)2 pastes may provide the
Ca2+ ions necessary for the growth and morphogenesis
of Candida. These mechanisms may explain why
Ca(OH)2 has been found to be ineffective against
C. albicans (Siqueira & Sen 2004).
Siqueira et al. (2001) investigated the antifungal
ability of several medicaments against C. albicans,
C. glabrata, C. guilliermondii, C. parapsilosis and S. cere-
visiae. They reported that whereas the paste of Ca(OH)2in CPMC/glycerine had the most pronounced antifun-
gal effects, Ca(OH)2 in glycerine or CHX and CHX in
detergent also had antifungal activity, but at a lower
level than the paste of Ca(OH)2 in CPMC/glycerine. In
another study, Ferguson et al. (2002) evaluated the
in vitro susceptibility of C. albicans to various irrigants
and medicaments. The minimum inhibitory concen-
trations of NaOCl, hydrogen peroxide, CHX digluconate
and aqueous Ca(OH)2 were determined. Their results
revealed that NaOCl, hydrogen peroxide and CHX
digluconate were effective against C. albicans, even
when diluted significantly. Furthermore, aqueous
Ca(OH)2 had no antifungal activity when maintained
in direct contact with C. albicans cells, whereas Ca(OH)2paste and CPMC were effective antifungal agents.
The antifungal effectiveness of CPMC was also
reported by Valera et al. (2001) who investigated the
effectiveness of several intracanal medicaments on
C. albicans harvested inside root canals, observing that
CPMC was the most effective, followed by Ca(OH)2/
CPMC paste. Siqueira et al. (2003) evaluated the
effectiveness of four intracanal medicaments in disin-
fecting the root dentine of bovine teeth experimentally
infected with C. albicans. Infected dentine cylinders
were exposed to four different medicaments: Ca(OH)2/
glycerine, Ca(OH)2/0.12% CHX digluconate, Ca(OH)2/
CPMC/glycerine and 0.12% CHX digluconate/zinc
oxide. Specimens were left in contact with the medica-
ments for 1 h, 2 and 7 days. The specimens treated
with Ca(OH)2/CPMC/glycerine paste or with CHX /zinc
oxide paste were completely disinfected after 1 h of
exposure. Ca(OH)2/glycerine paste only consistently
eliminated C. albicans infection after 7 days of expo-
sure. Ca(OH)2 mixed with CHX was ineffective in
disinfecting dentine even after 1 week of exposure. Of
the medicaments tested, the Ca(OH)2/CPMC/glycerine
paste and CHX digluconate mixed with zinc oxide were
the most effective in eliminating C. albicans cells from
dentine specimens.
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In summary, fungi have occasionally been found in
primary root canal infections, but they appear to occur
more often in filled root canals of teeth in which
treatment has failed. C albicans is by far the fungal
species most commonly isolated from infected root
canals. It seems that the combinations of Ca(OH)2 with
camphorated paramonochlorophenol or CHX have the
potential to be used as effective intracanal medicaments
for cases in which fungal infection is suspected.
Activity against biofilms
The term biofilm was introduced to designate the thin-
layered (sessile) condensations of microbes that may
occur on various surface structures in nature (Svens-
ater & Bergenholtz 2004). Free-floating bacteria exist-
ing in an aqueous environment, the so-called
planktonic form of microorganisms, are a prerequisite
for biofilm formation (Bowden & Hamilton 1998).
Biofilms may thus become established on any organic
or inorganic surface substrate where planktonic micro-
organisms prevail in a water-based solution (Stoodley
et al. 2004). In a dental context, a well-known and
extensively studied biofilm structure is established
during the attachment of bacteria to teeth to form
dental plaque (Svensater & Bergenholtz 2004). Here,
bacteria in saliva (planktonic organisms) serve as the
primary source of organisms for the organization of this
specific biofilm (Bowden & Hamilton 1998). In end-
odontics, the biofilm concept was initially discussed
mainly within the framework of bacteria on the root
tips of teeth with necrotic and infected pulps or pulpless
and infected root canal systems (Nair 1987, Nair et al.
2005). Such bacterial aggregations have been thought
to be the cause of therapy-resistant apical periodontitis
(Nair et al. 2005, Wu et al. 2006). Although not
described in as much detail, bacterial condensations
(that is, biofilms) on the walls of infected root canals
have been observed (Svensater & Bergenholtz 2004).
On the basis of transmission electron microscopy
(TEM), Nair (1987) examined the root canal contents
of 31 teeth, which had gross coronal caries and to
which the periapical inflammatory lesion was attached
upon extraction. In addition to his observations of the
microstructure of the inflammatory tissue, he noted
that the major bulk of the organisms existed as loose
collections of cocci, rods, filaments and spirochetes.
Whilst most of these organisms appeared suspended, in
what was described as a moist canal space, dense
aggregates were also observed sticking to the canal
walls and forming layers of bacterial condensations.
Amorphous material filled the inter-bacterial spaces
and was interpreted as an extracellular matrix of
bacterial origin. When they occurred, the bacterial
condensations had a palisade structure similar to the
one for dental plaque on external tooth surfaces,
suggesting similar mechanisms for bacterial attach-
ment as those for dental plaque. Sen et al. (1995)
examined untreated extracted teeth with apical peri-
odontitis by scanning electron microscopy (SEM) and
found that root canals were heavily infected with
microorganisms being observed in all areas of the
canal. Cocci and rods predominated and formed colo-
nies on the root canal walls and also, to a varying
degree, penetrated the dentinal tubules. Nair et al.
(2005) found that even after instrumentation, irriga-
tion and canal filling in a one-visit treatment, microbes
existed as biofilms in untouched locations in the main
canal, isthmuses and accessory canals in 14 of the 16
root filled teeth examined.
Anti-microbial agents have often been developed and
optimized for their activity against fast-growing, dis-
persed populations containing a single microorganism
(Gilbert et al. 1997, Svensater & Bergenholtz 2004).
However, microbial communities grown in biofilms are
remarkably difficult to eradicate with anti-microbial
agents and microorganisms in mature biofilms can be
notoriously resistant for reasons that have yet to be
adequately explained (Nair 1987, Bowden & Hamilton
1998). There are reports revealing that microorgan-
isms grown in biofilms could be 2-fold to 1000-fold
more resistant than the corresponding planktonic form
of the same organisms (Svensater & Bergenholtz 2004).
Using scanning electron microscopy and scanning
confocal laser microscopy, Distel et al. (2002) reported
that despite intracanal dressing with Ca(OH)2, E. fae-
calis formed biofilms in root canals. In another study,
Chai et al. (2007) reported that Ca(OH)2 was 100%
effective in eliminating E. faecalis biofilm. Brandle et al.
(2008) investigated the effects of growth condition
(planktonic, mono- and multi-species biofilms) on the
susceptibility of E. faecalis, Streptococcus sobrinus,
Candida albicans, Actinomyces naeslundii and Fusobacterium
nucleatum to alkaline stress. Findings demonstrated that
planktonic microorganisms were most susceptible; only
E. faecalis and C. albicans survived in saturated solution
for 10 min, the latter also for 100 min. Dentine
adhesion was the major factor in improving the
resistance of E. faecalis and A. naeslundii to calcium
hydroxide, whereas the multispecies context in a
biofilm was the major factor in promoting resistance
of S. sobrinus to the disinfectant. In contrast, the
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C. albicans response to calcium hydroxide was not
influenced by growth conditions.
In summary, the few studies conducted on the
antimicrobial potential of Ca(OH)2 on biofilms have
demonstrated inconsistent results. Further studies are
required to elucidate the anti-biofilm efficacy of
Ca(OH)2.
Clinical outcome studies on the use of Ca(OH)2medicaments
One-visit root canal treatment offers potential advan-
tages to both the dentist and patient (Ashkenaz 1984).
In addition to being less time-consuming and accepted
by patients (Sathorn et al. 2005), it prevents the
potential contamination or recontamination of the root
canal system between appointments (Ashkenaz 1984).
Root canal treatment on teeth with vital pulps should
ideally be completed in one session provided that the
time available, operators skills and anatomical condi-
tions are all favourable (Ashkenaz 1979). On the other
hand, root canal treatment in one session for teeth with
necrotic pulps, whether associated with a periradicular
lesion or not remains controversial (Siqueira 2001).
Two factors must be taken into account before
deciding upon a one-visit treatment of teeth with
necrotic pulps: the incidence of postoperative pain and
the long-term outcome of the treatment (Mohammadi
et al. 2006). Studies have found no difference in the
incidence of postoperative pain between one- and
multiple-visit root canal treatment (OKeefe 1976,
Mulhern et al. 1982, DiRenzo et al. 2002, Mohammadi
et al. 2006). Sathorn et al. (2008) reviewed systemat-
ically 16 studies with sample size varying from 60 to
1012 cases. The prevalence of postoperative pain
ranged from 3% to 58%. However, the heterogeneity
amongst the studies was too great to conduct a meta-
analysis and yield meaningful results. They concluded
that compelling evidence indicating a significantly
different prevalence of postoperative pain/flare-up of
either single- or multiple-visit root canal treatment was
lacking.
Therefore, the outcome of the root canal treatment
should be the major factor taken into account when
deciding the number of therapy sessions. Pekruhn
(1986) reported that there were significantly fewer
failures in the two-visit treatment group than in the
one-visit treatment group, regardless of the pretreat-
ment diagnosis. In a well-controlled clinical study,
Sjogren et al. (1997) investigated the role of infection
on the outcome of one-visit treatment after a follow-up
period of 5 years. Success was reported for 94% of the
infected root canals associated with periradicular
lesions that yielded negative culture at the time of
canal filling, whereas in the samples that yielded
positive culture prior to filling the success rate was
68%, thus stressing the need to have a negative culture
before canal filling in infected cases. In another clinical
study, Trope et al. (1999) evaluated radiographic
healing of teeth with periradicular lesions treated in
one or two visits. In the two-visit group, root canals
were medicated with Ca(OH)2 for at least 1 week. After
a 1-year follow-up, the additional disinfecting action of
calcium hydroxide resulted in a 10% increase in
healing rates. However, some of the teeth were not
associated with preoperative periapical lesions and
some cases treated over multiple visits had not been
dressed with an inter-appointment calcium hydroxide
medicament (the main biological purpose of multiple-
visit treatment). Katebzadeh et al. (1999, 2000) com-
pared periradicular repair radiographically and histo-
logically after root canal treatment of infected canals of
dogs performed in one or two sessions and reported
better results for the two-visit treatment in which
Ca(OH)2 was used as an intracanal disinfecting medi-
cament for 1 week.
On the other hand, several studies have concluded
that one-visit treatment was as effective as multiple-
visit treatment or even more effective. Weiger et al.
(2000) evaluated the influence of Ca(OH)2 as an inter-
appointment dressing on the healing of periapical
lesions associated with pulpless teeth. In both treat-
ment groups, the likelihood that the root canal
treatment yielded a success within an observation time
of 5 years exceeded 90%. However, a statistically
significant difference between the two treatment groups
was not detected. Furthermore, the probability that
complete periapical healing would take place increased
continuously with the length of the observation period.
Peters & Wesselink (2002) found no significant differ-
ences in healing of periapical radiolucency between
teeth that were treated in one visit (without) and two
visits with inclusion of Ca(OH)2 for 4 weeks. In a
randomized clinical trial, Molander et al. (2007)
assessed the 2-year clinical and radiographic outcome
of one- and two-visit root canal treatment and found
similar healing results. In a systematic review, Figini
et al. (2008) investigated whether the effectiveness and
frequency of short-term and long-term complications
were different when root canal treatment was com-
pleted in one or multiple visits. No detectable difference
in the effectiveness of root canal treatment in terms of
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International Endodontic Journal, 44, 697730, 2011 2011 International Endodontic Journal706
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radiologic success between single and multiple visits
was noted. In a randomized controlled clinical trial,
Penesis et al. (2008) compared radiographic periapical
healing after root canal treatment completed in one
visit or two visits with an interim calcium hydroxide/
CHX paste dressing and concluded that both treatment
options exhibited equally favourable periapical healing
at 12 months, with no statistically significant differ-
ence. In a systematic review, Sathorn et al. (2005)
compared the healing rate (as measured by clinical and
radiographic parameters) of single-visit root canal
treatment without calcium hydroxide dressing to
multiple-visit treatment with calcium hydroxide dress-
ing for 1 week. Single-visit root canal treatments were
marginally more effective than multiple visits, i.e. 6.3%
higher healing rate. However, the difference in healing
rate between these two treatment regimens was not
statistically significant.
In summary, the incidence of postoperative pain and
the long-term outcome of treatment must be taken into
account before deciding upon a one-visit or a multi-visit
treatment for teeth with necrotic pulps. There is no
compelling evidence to suggest a difference between the
regimens in terms of the prevalence of postoperative
pain/flare-up. There is still considerable controversy
concerning the effect of the number of treatment visits
on the biological outcome, whilst some studies support
two-visit treatment, other studies found that there was
no significant difference between the two treatment
modalities. It should be noted that some recent clinical
trials and systematic reviews found similar healing
results between one-visit and multiple-visit treatments.
Clearly, it is important to analyse the individual reports
included in systematic reviews and judge whether the
results are applicable (generalizable) to general dental
practice. In the majority of reports, the root canal
treatments were carried out in hospital settings by
specialist endodontists with the result that the conclu-
sions of such studies may not be relevant to conditions
prevailing in most general dental practices, where
resources and clinical expertize are often less favourable.
Buffering effect of dentine on Ca(OH)2
The root canal milieu is a complex mixture of a variety
of organic and inorganic components. Hydroxyapatite
is the major representative of the inorganic compo-
nents, whilst pulp tissue, micoorganisms and inflam-
matory exudate, rich in proteins such as albumin
(Haapasalo et al. 2007), are the major organic compo-
nents. The relative importance of the various organic
and inorganic compounds in the inactivation of root
canal disinfectants have been studied to a limited extent
only (Haapasalo et al. 2000). Difficulties in designing
experiments that will give reliable and comparable data
have been some of the greatest challenges. Haapasalo
et al. (2000) introduced a new dentine powder model
for studying the inhibitory effect of dentine on various
root canal irrigants and medicaments. They concluded
that dentine powder effectively abolished the killing of
E. faecalis by Ca(OH)2 (Haapasalo et al. 2000). On the
other hand, in the positive control group (absence of
dentine), saturated Ca(OH)2 killed E. faecalis cells in a
few minutes, whereas with the dentine powder added,
no reduction in the bacterial colony-forming units
could be measured even after 24 h of incubation with
Ca(OH)2. Hydroxyapatite had an effect similar to
dentine on Ca(OH)2, preventing the killing of E. faecalis
(Portenier et al. 2001). Initially, they used a high
concentration of dentine (18% w/v); however, in
another study they showed that even 1.8% dentine
(w/v) totally prevented the killing of E. faecalis by a
saturated Ca(OH)2 solution (Portenier et al. 2001).
The substantial effect of dentine on the antibacterial
activity of Ca(OH)2 can be attributed to the buffering
action of dentine against alkali (Wang & Hume 1988).
Ca(OH)2 is used as a thick paste in vivo; however, its
solubility is low and saturation is achieved in a
relatively low concentration of hydroxyl ions. Both
laboratory and in vivo studies have shown that buffer-
ing by dentine, particularly in the subsurface layers of
the root canal walls, might be the main factor behind
the reduced antibacterial effect of Ca(OH)2. It is possible
that deeper in dentine (outside the main root canal),
Ca(OH)2 is present as a saturated solution or at
concentrations even below that level (Haapasalo et al.
2000). Besides dentine, remnants of necrotic pulp
tissue as well as inflammatory exudate might affect the
antibacterial potential of endodontic disinfectants
(Haapasalo et al. 2007).
In summary, it seems that dentine, hydroxyapatite
and remnants of necrotic pulp tissue as well as
inflammatory exudate decrease the antibacterial
potential of Ca(OH)2. In other words, Ca(OH)2 is likely
to be effective under laboratory conditions but
relatively ineffective as a medicament in vivo.
Synergism between Ca(OH)2 and sodiumhypochlorite
Chemicals should be used to supplement mechani-
cal cleansing of canals, and irrigation with sodium
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2011 International Endodontic Journal International Endodontic Journal, 44, 697730, 2011 707
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hypochlorite and/or intracanal placement of Ca(OH)2are used as therapeutic agents in an attempt to alter the
properties of tissue remnants and microorganisms so as
to facilitate their removal/killing (Yang et al. 1995).
The synergy between Ca(OH)2 and sodium hypo-
chlorite is controversial. Hasselgren et al. (1988) stud-
ied dissolution of necrotic porcine muscle tissue and
reported that a paste of Ca(OH)2 powder and water was
capable of dissolving tissue after 12 days of exposure.
Furthermore, they reported an enhancement of the
tissue-dissolving capability of sodium hypochlorite
when the tissue was pretreated with Ca(OH)2 for
30 min, 24 h and 7 days. In another study, Metzler
& Montgomery (1989) demonstrated that long-term
(7 days) pretreatment with Pulpdent paste (Water-
town, MA, USA), a non-setting Ca(OH)2 paste, followed
by sodium hypochlorite irrigation cleaned canal isth-
muses in mandibular molars better than hand instru-
mentation alone. Yang et al. (1995) evaluated and
compared the tissue-dissolving properties of Ca(OH)2and NaOCl on bovine pulp tissue under both aerobic
and anaerobic conditions. Results demonstrated that
both agents partially dissolved pulp tissue and that the
anaerobic environment did not alter the tissue-dissolv-
ing properties of Ca(OH)2 or NaOCl. Furthermore, both
chemicals were equal and more effective than water
(control group). Wadachi et al. (1998) evaluated the
tissue-dissolving ability of NaOCl and Ca(OH)2 in a
bovine tooth model and reported that the amount of
debris was reduced remarkably in teeth treated with
NaOCl for >30 s or Ca(OH)2 for 7 days. However, the
combination of Ca(OH)2 and NaOCl was more effective
than the separate treatments. On the other hand, some
studies demonstrated that Ca(OH)2 was an ineffective
solvent of pulpal tissue. For example, Morgan et al.
(1991) reported that Ca(OH)2 as an irrigant resulted in
only 10% weight loss of bovine pulp tissue compared
with isotonic saline control.
In summary, the pretreatment of root canals
with Ca(OH)2 enhances the tissue-dissolving capability
of sodium hypochlorite, and this may confer an
advantage to multiple-visit root canal treatment where
NaOCl would be used following a period of Ca(OH)2medication.
Ca(OH)2 and chlorhexidine
Chlorhexidine is a cationic biguanide whose optimal
antimicrobial activity is achieved within a pH range of
5.57.0 (Athanassiadis et al. 2007). Therefore, it is
likely that alkalinizing the pH by adding Ca(OH)2 to
CHX will lead to precipitation of CHX molecules,
thereby decreasing its effectiveness (Mohammadi &
Abbott 2009). It has been demonstrated that the
alkalinity of Ca(OH)2 when mixed with CHX remained
unchanged (Haenni et al. 2003). Therefore, the useful-
ness of mixing Ca(OH)2 with CHX still remains unclear
and controversial (Athanassiadis et al. 2007).
When used as an intracanal medicament, CHX was
more effective than Ca(OH)2 in eliminating E. faecalis
from inside dentinal tubules (Athanassiadis et al.
2007). In a study by Almyroudi et al. (2002), all of
the CHX formulations used, including a CHX/Ca(OH)250 : 50 mix, were effective in eliminating E. faecalis
from dentinal tubules with a 1% CHX gel working
better than the other preparations. These findings were
corroborated by Gomes et al. (2006) in bovine dentine
and Schafer & Bossmann (2005) in human dentine
where 2% CHX gel had greater activity against
E. faecalis, followed by CHX/Ca(OH)2 and then Ca(OH)2alone.
In a study using agar diffusion, Haenni et al. (2003)
could not demonstrate any additional antibacterial
effect by mixing Ca(OH)2 powder with 0.5% CHX and
reported that CHX had a reduced antibacterial action.
However, Ca(OH)2 did not lose its antibacterial prop-
erties in such a mixture. This may be because of the
deprotonation of CHX at a pH >10, which reduces its
solubility and alters its interaction with bacterial
surfaces as a result of the altered charge of the
molecules. In a laboratory study using human teeth,
Ercan et al. (2006) reported that 2% CHX gel was the
most effective agent against E. faecalis inside dentinal
tubules, followed by a Ca(OH)2/2% CHX mixture,
whilst Ca(OH)2 alone was totally ineffective, even after
30 days. The 2% CHX gel was also significantly more
effective than the Ca(OH)2/2% CHX mixture against
C. albicans at 7 days, although there was no significant
difference at 15 and 30 days. Ca(OH)2 alone was
completely ineffective against C. albicans. In another
in vivo study using primary teeth, a 1% CHX-gluconate
gel, both with and without Ca(OH)2, was more effective
against E. faecalis than Ca(OH)2 alone over a 48-h
period (Oncag et al. 2006).
Schafer & Bossmann (2005) reported that 2% CHX-
gluconate was significantly more effective against
E. faecalis than Ca(OH)2 used alone or a mixture of
the two. Although this was also confirmed by Lin et al.
(2003), a study by Evans et al. (2003) using bovine
dentine concluded that 2% CHX with Ca(OH)2 was
more effective than Ca(OH)2 in water. In an animal
study, Lindskog et al. (1998) reported that teeth
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dressed with CHX for 4 weeks had reduced inflamma-
tory reactions in the periodontium (both apically and
marginally) and less root resorption. Waltimo et al.
(1999a) reported that 0.5% CHX-acetate was more
effective at killing C. albicans than saturated Ca(OH)2,
whilst Ca(OH)2 combined with CHX was more effective
than Ca(OH)2 used alone. The high pH of Ca(OH)2 was
unaffected when combined with CHX in this study.
In summary, although the usefulness of mixing
Ca(OH)2 with CHX remains unclear and controversial,
it seems that by mixing Ca(OH)2 with CHX the
antimicrobial activity of Ca(OH)2 is increased. In other
words, the descending order of the antimicrobial
activity of Ca(OH)2, CHX and their combination is as
follows: CHX, Ca(OH)2/CHX and Ca(OH)2.
Effect of Ca(OH)2 on dentine
Endodontic treatment of immature teeth with non-vital
pulps is a challenge. Apexification by Ca(OH)2 (Granath
1987, Frank 1966, Heithersay 1975) was based on the
concept of apical healing being promoted through the
induction of an apical barrier whilst at the same time
the high pH providing an antibacterial capability. The
flexural strength of dentine might, in part, depend on
an intimate link between two main components of
dentine, the hydroxyapatite crystals and the collage-
nous network. The organic matrix is composed of acid
proteins and proteoglycans containing phosphate and
carboxylate groups (Andreasen et al. 2002). These
substances may act as bonding agents between the
collagen network and the hydroxyapatite crystals
(Andreasen et al. 2002).
Rosenberg et al. (2007) measured the effect of
Ca(OH)2 on the microtensile fracture strength (MTFS)
of teeth and found that it was reduced by almost 50%
following 784 days of application. A study of bovine
dentine maintained in Petri dishes for 5 weeks con-
cluded that Ca(OH)2 reduced fracture strength by 32%
(White et al. 2002). Another study indicated that the
fracture strength of sheep dentine was reduced by 50%
following Ca(OH)2 treatment after 1 year (Andreasen
et al. 1989). Recently, Kawamoto et al. (2008) reported
that exposure to Ca(OH)2 paste significantly increased
the mean elastic modulus of bovine dentine, thereby
making it more prone to fracture.
Grigoratos et al. (2001) reported that treatment with
Ca(OH)2 reduced the flexural strength of dentine.
Andreasen et al. (2002) concluded that the fracture
strength of Ca(OH)2-filled immature teeth was halved
in approximately 1 year and attributed the frequent
reports of fractures of immature teeth filled with
Ca(OH)2 for extended periods to this factor. Doyon
et al. (2005) examined the resistance of human root
dentine to intracanal medication with Ca(OH)2 and
found that the fracture resistance of dentine was
decreased significantly after 6 months.
In summary, dentine exposed to Ca(OH)2 for an
extended period (6 months to 1 year) results in reduced
flexural strength and lower fracture resistance. There-
fore, other treatment modalities such as the apical
barrier technique using mineral trioxide aggregate
(MTA) should be used to manage teeth with non-vital
pulps and open apices, following a short period of
Ca(OH)2 medication where indicated.
Diffusion of hydroxyl ions through dentine
For calcium hydroxide to act effectively as an intra-
canal medicament, hydroxyl ions must be able to
diffuse through dentine. It might be expected that this
would occur in a manner similar to water, because
diffusion through dentine is primarily determined by
molecular weight (Nerwich et al. 1993). Several studies
have attempted to measure diffusion of hydroxyl ions
through dentine using a variety of experimental
approaches, including pH indicating solutions or papers
(Tronstad et al. 1981), pH measurement of ground
dentine (Wang & Hume 1988) and pH values of the
surrounding medium (Fuss et al. 1989).
Tronstad et al. (1981) examined histological sections
of monkey teeth 1 month following placement of a
Ca(OH)2 canal dressing and, using indicator solutions,
found that there was a pH gradient with high values
around the canal dressing towards the peripheral
dentine. The pH of cementum remained unchanged
but in resorption areas, where cementum was not
present, the increased pH extended to the dentine
surface. In another study related to the action of
Ca(OH)2 in cervical root resorption, Kehoe (1987)
placed Ca(OH)2 in the cervical part of the root canals
previously filled with bleaching agents and reported a
pH reversal from a slightly acidic to a slightly alkaline
level using pH electrodes and alkacid test papers.
Fuss et al. (1989) measured pH changes in distilled
water surrounding teeth filled with Ca(OH)2 and found
small changes in pH level up to 10 days. Wang &
Hume (1988) measured hydroxyl ion diffusion across
dentine between an occlusal cavity containing Ca(OH)2and a saline-filled pulp chamber at 16 days using a pH
meter. By taking ground dentine (subsequently mixed
with saline) from various depths, they demonstrated a
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gradient of pH values from the cavity layer decreasing
to the middle and pulpal layers, indicating slow
movement of hydroxyl ions through dentine. Nerwich
et al. (1993) investigated pH change over a 4-week
period after application of a Ca(OH)2 dressing and
concluded that hydroxyl ions derived from Ca(OH)2dressings diffused in a matter of hours into the inner
root dentine but required 17 days to reach the outer
root dentine and 23 weeks to reach peak levels.
Hydroxyl ions diffused faster and reached higher levels
cervically more than apically.
Gomes et al. (1996) reported diffusion of calcium
ions from Ca(OH)2 paste through dentine. Esberard
et al. (1996a) found that Ca(OH)2-containing sealers,
although suitable for use as root canal sealants, did not
produce an alkaline pH at the root surface. However, in
another study Ca(OH)2, as an intracanal medicament,
maintained a high pH at the root surface for at least
120 days (Esberard et al. 1996b). Calt et al. (1999)
demonstrated that, when non-setting Ca(OH)2 pastes
were applied to the root canal, diffusion of Ca2+
without an increase in pH in the surrounding media
occurred. Saif et al. (2008) indicated that a final canal
rinse with 3 mL 17% EDTA and 10 mL 6% NaOCl
before Ca(OH)2 placement allowed the greatest hydro-
xyl ion diffusion to the root surface.
In summary, it seems that diffusion of hydroxyl ions
through dentine depends on the period of medication,
diameter of dentinal tubules (cervical versus apical)
and smear layer removal (patency of dentinal tubules).
Furthermore, diffusion of hydroxyl ions through to
areas of root resorption where pH is acidic has a
positive effect on the progression of inflammatory root
resorption.
Removal of Ca(OH)2 from canals
Ca(OH)2 placed as a medicament has to be removed
before the canal is filled. Laboratory studies have
revealed that remnants of Ca(OH)2 can hinder the
penetration of sealers into the dentinal tubules (Calt &
Serper 1999), hinder the bonding of resin sealers to
dentine, increase the apical leakage of root fillings (Kim
& Kim 2002) and potentially interact with zinc oxide
eugenol sealers and make them brittle and granular
(Margelos et al. 1997). Therefore, complete removal of
Ca(OH)2 from the root canal before filling is recom-
mended.
Lambrianidis et al. (1999) evaluated the effectiveness
of removing Ca(OH)2 associated with several vehicles
from the root canal including normal saline, 3%
sodium hypochlorite (NaOCl), 3% NaOCl + 17% EDTA
as irrigants in combination with hand filing and found
that 45% of the canal surface area remained covered
with Ca(OH)2. They inferred that the amount of
Ca(OH)2 powder in the paste did not affect removal,
but the vehicle did. Margelos et al. (1997) revealed that
using 15% EDTA or NaOCl alone as irrigants did not
remove Ca(OH)2 from the root canal, but combining
these two irrigants with hand instrumentation
improved the effectiveness of removal.
Nandini et al. (2006) reported that the vehicle used
to prepare Ca(OH)2 paste was important for its removal.
Oil-based Ca(OH)2 paste was more difficult to remove
than Ca(OH)2 powder mixed with distilled water. Both
17% EDTA and 10% citric acid were found to remove
Ca(OH)2 powder mixed with distilled water, whereas
10% citric acid performed better than EDTA in remov-
ing an oil-based Ca(OH)2 paste. In another study,
Lambrianidis et al. (2006) compared the removal
efficiency of Ca(OH)2/CHX gel, Ca(OH)2/CHX solution
and Ca(OH)2/saline pastes using instrumentation with
or without a patency file and irrigation with NaOCl and
EDTA solutions. Remnants of medicaments were found
in all canals regardless of the experimental material or
use of patency filing. When examining the root canal as
a whole, Ca(OH)2/CHX gel paste was associated with
significantly larger amounts of residue, whereas the
Ca(OH)2/CHX solution paste was associated with less
residue than the other two groups with or without the
use of patency filing. They also noted that the use of
patency filing facilitated removal of more of the
medicament in the apical third of straight canals
(Lambrianidis et al. 2006).
Another method to remove remnants of Ca(OH)2from the root canal involved the use of ultrasonic
devices. Kenee et al. (2006) evaluated the amount of
Ca(OH)2 remaining in canals after removal with
various techniques including combinations of NaOCl
with EDTA irrigation, hand filing, rotary instrumenta-
tion, or ultrasonics. Overall, no technique removed the
Ca(OH)2 entirely. Rotary and ultrasonic techniques,
whilst not different from each other, removed signifi-
cantly more Ca(OH)2 than irrigant only techniques.
van der Sluis et al. (2007) evaluated the capacity to
remove a Ca(OH)2 paste from the root canal and the
efficacy of Ca(OH)2 removal during passive ultrasonic
irrigation using either sodium hypochlorite or water as
an irrigant. Results demonstrated that passive ultra-
sonic irrigation with 2% NaOCl was more effective in
removing Ca(OH)2 paste from artificial root canal
grooves than syringe delivery of 2% NaOCl or water
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International Endodontic Journal, 44, 697730, 2011 2011 International Endodontic Journal710
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as irrigant. Balvedi et al. (2010) found that neither
syringe injection nor passive ultrasonic irrigation were
efficient in removing inter-appointment intracanal
medicaments.
In summary, it seems that complete removal of
Ca(OH)2 paste from the root canal walls is not
achievable using routine techniques. However, the
type of vehicle used, use of patency filing and combin-
ing EDTA and NaOCl with hand instrumentation
improves the efficacy of Ca(OH)2 paste removal.
Furthermore, it seems that ultrasonic methods are
more efficient in removing Ca(OH)2 remnants than
passive irrigation.
Toxicity of Ca(OH)2 in medicaments
Early reports on the outcome of Ca(OH)2 extruded into
the periapical region concluded it was well tolerated
and was resorbed (Martin & Crabb 1977). However, the
periapical response to Ca(OH)2 based on results from
other reports seems to be equivocal.
Spangberg (1969) reported an inflammatory re-
sponse with inhibited bone healing 2 weeks after the
implantation of Ca(OH)2 into guinea-pig bone; never-
theless, it was found to be one of the least irritating
root-filling materials and was replaced by new bone
within 12 weeks of placement.
However, Ca(OH)2 has been reported to have a
detrimental effect on periodontal tissues when used as
an intracanal medicament during root canal treatment
(Hauman & Love 2003). Blomlof et al. (1988) observed
that Ca(OH)2 could negatively influence marginal soft
tissue healing and suggested the completion of root
canal treatment prior to the removal of cementum as
might occur during periodontal therapy. Breault et al.
(1995) reported that the use of Ca(OH)2 demonstrated
a decreased but not statistical significant inhibition of
attached human gingival fibroblasts (HGF) and pro-
posed that Ca(OH)2 should be avoided as an interim
medicament when trying to regenerate or establish
new attachment in tissues adjacent to endodontically
involved teeth. Contrary to these findings, Hammar-
strom et al. (1986) demonstrated that Ca(OH)2 did not
affect the healing of replanted monkey teeth with intact
cementum and only temporarily in those undergoing
cemental repair. Similarly, Holland et al. (1998)
observed that periodontal healing associated with
infected root canals filled with Ca(OH)2 was not
hindered 6 months after experimental periodontal sur-
gical injury in dogs. Barnhart et al. (2005) found that
Ca(OH)2 was well tolerated by HGF. Ribeiro et al.
(2004) found that Ca(OH)2 did not promote DNA
damage in mammalian cells. Pissiotis & Spangberg
(1990) evaluated mandible bone reactions of guinea
pigs to implants of hydroxyapatite, collagen, and
Ca(OH)2, alone or in different combinations, over a
period of 16 weeks. Findings revealed that no major
inflammatory reactions occurred in any of the implant
combinations. Hydroxyapatite was not resorbed over
the examination periods, but Ca(OH)2 and collagen
implants were partially or totally resorbed and replaced
by bony tissue. Wakabayashi et al. (1995) evaluated
the effect of a Ca(OH)2 paste dressing on uninstru-
mented root canal walls and found that it could
dissolve the odontoblastic cell layer, but had little effect
on predentine. Holland et al. (1999) reported that rat
subcutaneous connective tissue reaction to Ca(OH)2and MTA inside the dentine tubes was desirable. They
observed the formation of calcite granulations, bire-
fringent to polarized light, near the lumen of dentinal
tubule in Ca(OH)2 samples. Under these granulations, a
von Kossa-positive bridge of hard tissue was formed. In
MTA samples, the same granulations was observed, but
their number was less than the Ca(OH)2 group.
Furthermore, contrary to the Ca(OH)2 group, the
calcite granulations were in contact with MTA. This
may be because of the similarity of the mechanism of
action of MTA and Ca(OH)2; the calcium oxide in the
MTA powder is converted into Ca(OH)2 when the paste
is prepared with water. In contact with tissue fluids,
this mixture would dissociate into calcium and hydro-
xyl ions. The calcium ions reacting with the carbonic
gas of the tissues would originate the calcite granula-
tions. Close to these granulations, there is accumula-
tion of fibronectin, which allows cellular adhesion and
differentiation. Guigand et al. (1999) confirmed the
cytocompatibility of Ca(OH)2 and a calcium oxide-
based compound.
In summary, it seems that Ca(OH)2 paste is well
tolerated by bone and dental pulp tissues. However, its
effect on the periodontal tissue is controversial.
Calcium hydroxide when used in sealersduring root canal treatment
Sealers are responsible for the principal functions of a
root filling, namely, sealing the root canal system,
entombment of remaining bacteria and the filling of
irregularities in the canal system (rstavik 2005).
Several different chemical formulations have served as
bases for root canal sealers and the success of Ca(OH)2as a pulp-capping agent and as an inter-appointment
Mohammadi & Dummer Calcium hydroxide in endodontics and dental traumatology
2011 International Endodontic Journal International Endodontic Journal, 44, 697730, 2011 711
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medicament prompted its use in sealer cement formu-
lations. Sealapex (SybronEndo, Orange County, CA,
USA) and Apexit (Ivoclar Vivadent Inc., Schaan,
Liechtenstein) are brand names of this type of material
(rstavik 2005).
Leakage
Limkangwalmongkol et al. (1991) assessed the apical
leakage of four root canal sealers when used with
laterally compacted Gutta-percha using dye penetra-
tion and concluded that the distance dye penetrated the
canals was as follows: Apexit (Ivoclar Vivadent),
1.67 mm; Sealapex (SybronEndo), 2.28 mm; Tubliseal
(SybronEndo), 1.95 mm; AH26 (Dentsply de Trey,
Konstanz, Germany), 0.82 mm; and Gutta-percha
alone, 8.37 mm. Sleder et al. (1991) reported that
Sealapex had a sealing ability comparable to Tubliseal.
In a laboratory study, Siqueira et al. (1999) evaluated
the coronal leakage of human saliva into root canals
filled using lateral compaction of Gutta-percha and one
or other of two Ca(OH)2-based sealers and found that
35% of the Sealer 26 (Dentsply, Petropolis, Brazil)
samples and 80% of the Sealapex samples were entirely
recontaminated at 60 days. Using dye penetration
methods, Ozata et al. (1999) compared the apical
leakage of Ketac-Endo (ESPE GmbH & Co., Seefeld-
Oberbay, Germany), Apexit (Ivoclar Vivadent) and
Diaket (3M/ESPE, Minneapolis, MN, USA) and found
that there was no significant difference between Apexit
and Diaket. However, there was significantly more
leakage with Ketac-Endo. Timpawat et al. (2001)
concluded that coronal bacterial leakage of canals
filled with a Ca(OH)2-based sealer (Apexit) was signif-
icantly greater than those filled with a resin-based
sealer (AH26). Economides et al. (2004) found that
apical sealing ability of Fibrefill (a resin-based sealer)
(Pentron, Wallingford, CT, USA) was significantly
better than CRCS (Colte`ne Whaledent/Hygenic, Mah-
wah, NJ, USA). In another study Cobankara et al.
(2006) concluded that the apical sealing ability of
Sealapex was significantly better than three other
sealers (Rocanal 2, La Maison Dentaire SA, Balzers,
Switzerland; AH-Plus, Dentsply De Trey, and RC sealer,
Sun Medical Co Ltd, Shiga, Japan) at 7, 14 and
21 days. Siqueira et al. (1999) found that during a 60-
day period, Sealer 26 (Dentsply, Industria e Comercio
Ltda, Petropolis, Brazil) resulted in significantly less
leakage than Sealapex. Pommel et al. (2003) found
that there was no statistically significant difference
amongst AH26, Pulp Canal Sealer, and Ketac-Endo. In
a laboratory study, Cobankara et al. (2006) evaluated
the apical seal obtained with four root canal sealers
(Rocanal 2, Sealapex, AH-Plus, and RC Sealer) and
reported that apical leakage associated with all sealers
decreased gradually from 7 to 21 days. Sealapex had
better apical sealing than the other sealers at 7, 14 and
21 days. RC Sealer, AH Plus and Rocanal 2 had similar
apical leakage values at every period. It has been
demonstrated that the long-lasting seal of these mate-
rials may, amongst other influencing factors, depend
on their thickness and solubility (Wu et al. 1995).
Considering that the main purpose of using sealers is
to fill gaps within the irregular root canal system, their
solubility and disintegration should be as low as
possible. On the other hand, to achieve favourable
effects, Ca(OH)2 should dissociate into calcium and
hydroxyl ions, which is in contrast to the philosophy of
using sealers. Therefore, a major dilemma arises
regarding both the long-term sealing ability and
favourable biological properties of Ca(OH)2-based
sealers.
In summary, the sealing ability of Ca(OH)2-based
sealers compared to other sealers is ambiguous. This
may be because of factors such as the method used to
evaluate leakage and the often limited sample sizes
included. However, it is clear that there is no superi-
ority for Ca(OH)2-based sealers over other groups of
sealers.
Biocompatibility
There are five approaches to assess the biocompatibility
of endodontic materials such as sealers: cytotoxic
evaluation, genotoxicity, subcutaneous implants,
intraosseous implants, usage tests and human studies
(H